This research is designed to identify the adaptive mechanisms that allow a mammalian free muscle graft to survive the early post-transplantation period and become structurally and functionally reintegrated with the host. We plan to test the hypothesis that the success of free muscle grafts is due primarily to the breakdown of old muscle fibers and the regeneration of new muscle rather than to the survival of the original muscle fibers. Rat muscles will be pretreated by denervation (the standard clinical pretreatment), Marcaine and ischemia to determine if all methods are acting through a morphological common denominator, namely the establishment of an increased supply of precursor myogenic cells, to allow successful free grafting. Pre-treated, nontransplanted muscles will be examined electron microscopically to determine numbers of satellite cells. Early grafted rat extensor digitorum longus and soleus muscles will be examined by electron and intravital microscopy to determine degeneration patterns of old muscle fibers, myoblast populations and vascular pattern. Older grafts will be examined morphologically and histochemically for nerve fiber return and motor end plate formation. In addition they will be stimulated through the nerve to find out when the grafts have become functionally reintegrated with the nervous system. Understanding of these early adaptive mechanisms in freely grafted muscles will allow more rational surgical approaches to free muscle transplantation in man.